Cholesterol efflux capacity, high-density lipoprotein function, and atherosclerosis.

Area of Science:

• Cardiovascular Medicine
• Biochemistry
• Lipid Metabolism

Background:

• High-density lipoprotein (HDL) plays a role in cardiovascular protection via reverse cholesterol transport.
• The capacity of HDL to accept cholesterol from macrophages is hypothesized to predict atherosclerotic burden.

Purpose of the Study:

• To investigate whether cholesterol efflux capacity predicts atherosclerotic burden.
• To determine the association between cholesterol efflux capacity and measures of atherosclerosis, including carotid intima-media thickness and coronary artery disease.

Main Methods:

• Cholesterol efflux capacity was measured ex vivo in macrophages incubated with apolipoprotein B-depleted serum from participants.
• Participants included 203 healthy volunteers, 442 patients with coronary artery disease, and 351 patients without coronary artery disease.
• Carotid artery intima-media thickness was assessed in healthy volunteers.

Main Results:

• Cholesterol efflux capacity was inversely associated with carotid intima-media thickness and coronary artery disease status.
• This association remained significant independently of HDL cholesterol and apolipoprotein A-I levels.
• Pioglitazone treatment enhanced efflux capacity in patients with metabolic syndrome and low HDL, while statins did not in hypercholesterolemia patients.

Conclusions:

• Cholesterol efflux capacity is a functional metric of HDL.
• HDL cholesterol efflux capacity is a strong predictor of carotid intima-media thickness and coronary artery disease.
• This functional measure is independent of HDL cholesterol levels.